Nature 501: 380–384
Somatic stem cell activity is critical for tissue homeostasis. Defects in stem cells are thought to be involved in many diseases, including inherited disorders and aging (He et al, 2009). In a recent paper published in Nature, Adorno et al (2013) demonstrate that there is a general somatic stem cell defect in Down syndrome (DS), a congenital disorder with triplication of human chromosome 21 (HSA21; Roper and Reeves, 2006; Mégarbané et al, 2009). They report that the deubiquitinase Usp16 gene located on HSA21 is a key epigenetic switch that regulates stem cell self-renewal and senescence in DS, and suggest that inhibiting or reducing HSA21 may be beneficial in treating the sequelae of DS.